It is our hypothesis that alcohol abuse leads to the depletion of polyunsaturated lipids from many tissues and leads to altered metabolism of eicosanoids. Such changes in the liver as well as in other organs and tissues may cause or contribute to the pathological changes associated with alcoholism. Previously, we have shown that there are losses in arachidonic acid (20:4n6) and other n-6 fatty acids in alcohol exposed rat tissues as well as in the blood cells of alcoholics. The distribution of both the alcohol-induced losses in polyunsaturated fatty acids (PUFA) and the preventive effects of dietary elevations in specific fatty acids have been studied in detail in rat liver lipids. Changes in the total lipid extracts can be ascribed to alterations in the phospholipid and cholesterol ester classes but there was little change as a result of ethanol inhalation in the triglyceride or nonesterified fatty acid pools. Animals fed borage oil rich in 18:3n6 during the ethanol inhalation period (7 d) did not have as great a loss in 20:4n6 than those fed 18:1n9 or long chain n-3 fatty acid based diets. Similarly, losses in n-3 fatty acids subsequent to alcohol exposure were not as great in animals fed a menhaden oil based diet. These "protective" effects of fatty acid supplementation were also traced mainly to the phospholipid and cholesterol ester pools. cats fed alcohol once daily for 12 weeks showed a progressive lsos of long chain polyunsaturates including 20:4n6 and 22:6n3 with a concomitant increase in 18:2n6 and non-essential fatty acids in plasma. Liver biopsies showed a loss in nearly all of the polyunsaturates after 9 days of alcohol exposure. This study indicated that cats placed on a diet that is only just adequate in supplying fatty acids and exposed to chronic alcohol may provide an excellent model for the study of brain and liver pathology related to human alcoholism.